DESCRIPTION: The primary aim of this proposal is to participate in a multi-site cooperative study to assess the efficacy of combined behavioral and pharmacologic interventions in the treatment of alcohol dependence. As stated in RFA AA-97-004, the goal of the research is to determine if improvement in treatment outcomes can be achieved by implementing therapeutic strategies that integrate various combinations of pharmacotherapy and behavioral interventions. We specifically propose a 2x2x2 factorial design study testing the combination of two pharmacotherapies, their associated placebos, and two behavioral therapies in a sample of 720 subjects (90 subjects per site at each of 8 sites). The pharmacotherapy conditions are (1) naltrexone plus placebo; (2) acamprosate plus placebo; (3) naltrexone plus acamprosate; and (4) placebo plus placebo. The behavioral therapy conditions are (1) brief alcohol counseling (BAC) and (2) motivational enhancement therapy plus cognitive-behavioral coping skills therapy (MET/CBT). Subjects will be randomized with equal probability to one of the following eight treatment cells: 1) naltrexone + acamprosate + BAC; 2) naltrexone + BAC; 3) acamprosate + BAC; 4) placebo + BAC; 5) naltrexone + acamprosate + MET/CBT; 6) naltrexone + MET/CBT; 7) acamprosate + MET/CBT; and 8) placebo + MET/CBT. The study will be conducted in two phases: a six-month active treatment phase and a 12-month posttreatment follow-up phase. The primary measure of drinking outcome throughout the study will be the percentage of days that subjects are abstinent (P.A.). In addition to the main study, we will perform a preliminary study to evaluate whether or not the toxic effects of alcohol are exacerbated by taking a naltrexone/acamprosate combination. We will study this by assessing psychomotor performance and physiological activity after a controlled alcohol challenge in 20 subjects before and after they have taken this medication combination for one week. Subjects in the preliminary study will be occasional drinkers who do not meet criteria for alcohol abuse or dependence. The preliminary study will inform the main trial by enabling the study investigators to learn about the potential effects of combining these two medications with alcohol.